iRQC, a surveillance pathway for 40S ribosomal quality control during mRNA translation initiation
| Autor: | Eric J. Bennett, J. Wade Harper, Alison Vicary, Danielle M. Garshott, Heeseon An, Marilyn Leonard, Elayanambi Sundaramoorthy |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Ribosomal Proteins
ribosome-associated quality control 1.1 Normal biological development and functioning Messenger Medical Physiology Small translation initiation Ribosome Article General Biochemistry Genetics and Molecular Biology Eukaryotic translation Underpinning research Ribosomal protein RNF10 ubiquitin Ribosome Subunits Genetics Humans Eukaryotic Small Ribosomal Subunit RNA Messenger Peptide Chain Initiation Translational Ribosome Subunits Small Eukaryotic protein homeostasis biology Eukaryotic Large Ribosomal Subunit Chemistry Translational Ubiquitination Translation (biology) HCT116 Cells Ubiquitin ligase Cell biology Proteostasis HEK293 Cells Peptide Chain Initiation Proteolysis Transcription preinitiation complex biology.protein RNA Eukaryotic Generic health relevance Biochemistry and Cell Biology Carrier Proteins Ubiquitin Thiolesterase |
| Zdroj: | Cell reports, vol 36, iss 9 Cell Rep |
| DOI: | 10.1101/2021.04.20.440649 |
| Popis: | SummarySince multiple ribosomes can engage a single mRNA, nonuniform ribosome progression can result in collisions. Ribosome collisions during translation elongation elicit a multifaceted ribosome-associated quality control (RQC) response. Despite advanced mechanistic understanding of translation initiation, a parallel RQC pathway that acts on collided preinitiation complexes has not been described. Here, we show that blocking progression of scanning or elongating ribosomes past the start codon triggers uS3 and uS5 ribosomal ubiquitylation. We demonstrate that conditions that activate the integrated stress response can also induce preinitiation complex collisions. The ubiquitin ligase, RNF10, and the deubiquitylating enzyme, USP10, are the key regulators of uS3 and uS5 ubiquitylation. Prolonged uS3 and uS5 ubiquitylation results in 40S, but not 60S, ribosomal protein degradation in an autophagy-independent manner. This study identifies a distinct arm in the RQC pathway, initiation RQC (iRQC), that acts on pervasive ribosome collisions during translation initiation to modulate translation activity and capacity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|